In-hospital outcomes and postdischarge mortality in patients with acute coronary syndrome and atrial fibrillation.

BACKGROUND: It is unclear whether advances in management of acute coronary syndrome (ACS) and introduction of novel oral anticoagulants have changed outcomes in patients with ACS with concomitant atrial fibrillation (AF). OBJECTIVE: This study aimed to examine the incidence of AF in patients admitted for ACS and to evaluate its association with adverse outcomes, given the recent advances in management of both diseases. METHODS: Natural language processing search algorithms identified AF in patients admitted with ACS across 13 Northwell Health Hospitals from 2015 to 2021. Hierarchical generalized linear mixed modeling was used to assess the association between AF and in-hospital mortality, bleeding, and stroke outcomes; marginal Cox regression modeling was used to assess the association between AF and postdischarge mortality. RESULTS: Of 12,315 patients admitted for ACS, 3018 (24.5%) had AF with 1609 (53.3%) newly diagnosed. AF patients more commonly received anticoagulation with an oral anticoagulant (80.4% vs 12.3%) or heparin (61.9% vs 56.9%), had lengthier intensive care unit stay (72 vs 49 hours), and underwent fewer percutaneous coronary interventions (31.9% vs 53.1%). In-hospital bleeding, stroke, and mortality were higher in the AF group (15.3% vs 5.0%, 7.4% vs 2.4%, and 6.9% vs 2.1%, respectively). AF was an independent risk factor for all in-hospital outcomes (odds ratios of 2.5, 2.7, and 2.0 for bleeding, stroke, and mortality, respectively) as well as for postdischarge mortality (hazard ratio, 1.3; 95% CI, 1.2-1.5). CONCLUSION: AF is present in 25% of ACS patients and increases risk of in-hospital and postdischarge adverse outcomes. Additional data are required to direct optimal management.

Atrial Fibrillation and Dementia: Pathophysiological Mechanisms and Clinical Implications.

Numerous longitudinal studies suggest a strong association between cardiovascular risk factors and cognitive impairment. Individuals with atrial fibrillation are at higher risk of dementia and cognitive dysfunction, as atrial fibrillation increases the risk of cerebral hypoperfusion, inflammation, and stroke. The lack of comprehensive understanding of the observed association and the complex relationship between these two diseases makes it very hard to provide robust guidelines on therapeutic indications. With this review, we attempt to shed some light on how atrial fibrillation is related to dementia, what we know regarding preventive interventions, and how we could move forward in managing those very frequently overlapping conditions.

Atrial fibrillation in the setting of cardiac amyloidosis - A review of the literature.

Cardiac amyloidosis (CA) is related to the aggregation of insoluble fibrous deposits of misfolded proteins within the myocardium. Transthyretin amyloidosis (ATTR) and immunoglobulin light-chain amyloidosis are the main forms of CA. Atrial fibrillation (AF) is a common arrhythmia in CA patients, especially in those with ATTR amyloidosis. Increased atrial preload and afterload, atrial enlargement, enhanced atrial wall stress, and autonomic dysfunction are the main mechanisms of AF in CA patients. CA is associated with the formation of endocardial thrombi and systemic embolism. The promoters of thrombogenesis include endomyocardial damage, blood stasis, and hypercoagulability. The prevalence of thrombi in patients with AF remains elevated despite long-term anticoagulation. Consequently, transesophageal ultrasound examinations before cardioversion should be performed to exclude endocardiac thrombi despite anticoagulation. Furthermore, the CHA2DS2-VASc score should not be used to assess the thromboembolic risk in CA patients with AF. Rate control is challenging in patients with CA, while rhythm control is the preferred treatment option, especially in the early stages of the disease process. Although catheter ablation is an effective treatment option, more data are needed to explore the role of the procedure in CA patients.

MicroRNAs are associated with cardiac biomarkers, cardiac structure and function and incident outcomes in heart failure.

AIMS: The association between microRNAs (miRNAs) and established cardiac biomarkers is largely unknown. We aimed to measure the association between plasma miRNAs and N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin I, soluble urokinase-type plasminogen activator receptor (suPAR), and galectin-3 with cardiac structure and function and clinical outcomes. METHODS AND RESULTS: We quantified 32 plasma miRNAs using the FirePlex miRNA assay and measured biomarkers in 139 individuals with symptomatic heart failure (HF). We used principal component (PC) analysis and linear regression to evaluate the association between miRNAs and biomarkers with ventricular size and function by echocardiography and Cox modelling for the incidence of a first composite event of HF hospitalization, heart transplant, left ventricular assist device implant, or death. The mean (standard deviation) age at baseline was 64.3 (12.4) years, 33 (24%) were female, and 122 (88%) were White. A total of 45 events occurred over a median follow-up of 368 (interquartile range 234, 494) days. Baseline NT-proBNP (ß = -2.0; P = 0.001) and miRNA PC2 (ß = 2.6; P = 0.002) were associated with baseline left ventricular ejection fraction. NT-proBNP (ß = 20.6; P = 0.0004), suPAR (ß = -39.6; P = 0.005), and PC4 (ß = 21.1; P = 0.02) were associated with baseline left ventricular end-diastolic volumes. NT-proBNP [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.28-2.18, P = 0.0002], galectin-3 (HR 2.02, 95% CI 1.05-3.91, P = 0.036), PC3 (HR 1.75, 95% CI 1.23-2.49, P = 0.002), and PC4 (HR 1.67, 95% CI 1.1-2.52, P = 0.016) were independently associated with incident events. CONCLUSIONS: Biomarkers and miRNA PCs are associated with cardiac structure and function and incident cardiovascular outcomes. Combining information from miRNAs provides prognostic information beyond biomarkers in HF.

Differences between Lower Extremity Arterial Occlusion vs. Stenosis and Predictors of Successful Endovascular Interventions.

Background and Objectives: In patients with peripheral artery disease, there is insufficient understanding of characteristics that predict successful revascularization of the lower extremity (LE) chronic total occlusions (CTOs) and baseline differences in demographic, clinical, and angiographic characteristics in patients with LE CTO vs. non-CTO. We aim to explore these differences and predictors of successful revascularization among CTO patients. Materials and Methods: Two vascular centers enrolled LE-CTO patients who underwent endovascular revascularization. Data on demographics, clinical, angiographic, and interventional characteristics were collected. LE non-CTO arterial stenosis patients were compared. A total of 256 patients with LE revascularization procedures were studied; among them, 120 had CTOs and 136 had LE stenosis but no CTOs. Results: Aspirin use (Odds ratio, OR: 3.43; CI 1.32-8.88; p = 0.011) was a positive predictor whereas a history of malignancy (OR: 0.27; CI 0.09-0.80; p = 0.018) was a negative predictor of successful crossing in the CTO group. The CTO group had a higher history of myocardial infarction (29.2 vs. 18.3%, p = 0.05), end-stage renal disease (19.2 vs. 9.6%, p = 0.03), and chronic limb-threatening ischemia as the reason for revascularization (64.2 vs. 22.8%, p < 0.001). They were more likely to have advanced TransAtlantic Inter-Society Consensus (TASC) stages, multi-vessel revascularization procedures, longer lesions, and urgent treatment. Conclusions: The use of aspirin is a positive predictor whereas a history of malignancy is a negative predictor for successful crossing in CTO lesions. Additionally, LE-CTO patients have a higher incidence of comorbidities, which is expected given their higher disease burden. Successful endovascular re-vascularization can be associated with baseline clinical variables.

Lady Windermere syndrome with haemoptysis: suspected pulmonary aspergilloma and MAC pulmonary disease.

We present a case of a woman in her 70s, with a history of Mycobacterium avium complex (MAC) pulmonary disease, pectus excavatum, s-shaped thoracolumbar scoliosis, bronchiectasis of the right middle lobe, lingula of left upper lobe, and malnutrition with low body mass index of 14 kg/m2, who presented to the hospital due to worsening shortness of breath and small volume haemoptysis over 2 weeks. The patient was diagnosed with pulmonary MAC infection for the first time in 1999 without known history of pulmonary disease. Later on, it was complicated by massive haemoptysis requiring bronchial artery embolisation; however, she was unable to complete an oral antibiotic regimen due to gastrointestinal adverse reactions. Chest CT identified a newly found mass in the left upper lobe bulla, consistent with a radiological finding of aspergilloma. We present a rare symptoms constellation, described as 'Lady Windermere syndrome' and chronic untreated MAC infection progressing from reticulonodular changes to fibrocavitary lung disease and suspected aspergilloma formation.

Comparison of in-hospital outcomes and complications of leadless pacemaker and traditional transvenous pacemaker implantation.

AIMS: Since their introduction in 1958, traditional cardiac pacemakers have undergone considerable upgrades over the years, but they continue to have a complication rate of ∼3.8%-12.4%. There are no randomized controlled trials comparing outcomes of leadless pacemakers (LPM) with single-chamber transvenous pacemakers (TV-VVI). The aim is to assess the differences in the procedural complications and in-hospital outcomes between LPM and TV-VVI implants. METHODS AND RESULTS: We queried the national inpatient database from 2016 to 2019 to include adult patients undergoing LPM and TV-VVI. Admissions for leadless and single-lead transvenous pacemakers were identified by their appropriate ICD-10 codes. Complications were identified using ICD-10 codes that mostly represent initial encounter. The difference in outcomes was assessed using multivariable logistic regression and 1:1 propensity score matching between the two cohorts. Thirty-five thousand four hundred thirty expanded samples of admissions were retrieved of which 27 650 (78%) underwent TV-VVI with a mean age 81.3 ± 9.4 years and 7780 (22%) underwent LPM with a mean age of 77.1 ± 12.1 years. The LPM group had a higher likelihood of in-hospital mortality [adjusted odds ratio (aOR): 1.63, 95% CI (1.29-2.05), P < 0.001], vascular complications [aOR: 7.54, 95% CI (3.21-17.68), P < 0.001], venous thromboembolism [aOR: 3.67, 95% CI (2.68-5.02), P < 0.001], cardiac complications [aOR: 1.79, 95% CI (1.59-2.03), P < 0.001], device thrombus formation [aOR: 5.03, 95% CI (2.55-9.92), P < 0.001], and need for a blood transfusion [aOR: 1.54, 95% CI (1.14-2.07), P < 0.005]. The TV-VVI group had higher likelihood of in-hospital pulmonary complications [aOR:0.68, 95% CI (0.54-0.87), P < 0.002] and had a need for device revisions [aOR:0.42, 95% CI (0.23-0.76), P < 0.004]. CONCLUSION: There is a higher likelihood of all-cause in-hospital mortality and complications following LPM implantation in comparison to TV-VVI. This could be related to higher co-morbidities in the LPM group. Clinical trials aimed to accurately compare these two groups should be undertaken.

A Case of Type V Hyperlipoproteinemia Resistant to Insulin Treatment.

Type V hyperlipoproteinemia or multifactorial chylomicronemia syndrome is a rare lipid disorder triggered mainly by uncontrolled diabetes, obesity, poor diet, or particular medications. It is associated with an increased risk of acute pancreatitis and accelerated coronary artery disease which may manifest in younger age groups. We present a case of a 42-year-old male who presented to the emergency department (ED) complaining of a non-healing hand injury. Upon laboratory workup, the patient was found to have an elevated total cholesterol (TC) of 1129 mg/dL, very low levels of high-density lipoprotein (HDL) and triglycerides (TG) > 4000 mg/dL with an inability to calculate low-density lipoprotein (LDL). Lipoprotein electrophoresis revealed an actual TG level of > 7000 mg/dL, increased chylomicrons, normal B and pre-B-lipoproteins, and increased L-lipoproteins with an elevated Apolipoprotein B. Despite these derangements, the patient did not exhibit any abdominal complaints, demonstrating a normal lipase level. The physical exam was indicative of bilateral arcus senilis and obesity. Insulin drip was initiated along with intravenous (IV) hydration and it required 12 days to bring triglycerides down to less than 1000 mg/dL. The total cholesterol was also seen to be down trending to around 500 mg/dL and the HDL improved to 22 mg/dL. We present this case as a unique presentation of asymptomatic chylomicronemia resistant to insulin treatment with an elevated ApoB but with no evidence of pancreatitis or coronary artery disease.

Venous Thromboembolism in Pregnancy: Challenges and Solutions.

Venous thromboembolism (VTE) is a serious medical condition that can lead to severe morbidity and mortality, making it a significant public health concern. VTE is a multifactorial condition that results from the interaction of genetic, acquired, and environmental factors. Physiological changes during pregnancy increase the risk of VTE as they express Virchow's triad (increased coagulation factors, decreased fibrinolysis, trauma, and venous stasis). Moreover, pregnancy-related risk factors, such as advanced maternal age, obesity, multiple gestations, and cesarean delivery, further increase the risk of VTE. Managing VTE in pregnancy is challenging due to the complexity of balancing the risks and benefits of anticoagulant therapy for both the mother and the fetus. A multidisciplinary approach involving obstetricians, hematologists, and neonatologists, is necessary to ensure optimal outcomes for both the mother and baby. This review aims to discuss the current challenges associated with VTE in pregnancy and identify potential solutions for improving outcomes for pregnant women at risk for VTE.

Outcomes of Non-ST-Segment Myocardial Infarction During Chronic Heart Failure and End-Stage Renal Disease.

Non-ST-segment myocardial infarction (NSTEMI) occurs frequently in a growing population of patients with chronic heart failure (HF) and end-stage renal disease (ESRD) but outcomes with invasive management approaches are unknown. We sought to determine in-hospital outcomes with percutaneous coronary intervention (PCI) in comparison with medical management only. The National Inpatient Sample was used to capture hospitalizations in the United States from 2006 to 2019. Admissions for NSTEMI in patients with chronic HF and ESRD were identified by International Classification of Diseases codes. The cohort was divided into those that received PCI or medical management only. In-hospital outcomes were compared by multivariable logistic regression and propensity matching. In 27,433 hospitalizations, 8,004 patients (29%) underwent PCI, and 19,429 (71%) were managed with medications only. PCI was associated with lower adjusted odds of death during hospitalization (adjusted odds ratio 0.59, 95% confidence interval 0.52 to 0.66, p <0.01). This association remained consistent after propensity matching (adjusted odds ratio 0.56, 95% confidence interval 0.49 to 0.64, p <0.01) and was apparent across all subtypes of HF. Patients with PCI had greater duration (5, 3, to 9 vs, 5, 3 to 8 days, p <0.01) and cost of hospitalization ($107,942, 70,230 to $173,182 vs, $44,156, 24,409 to $80,810, p <0.01). In conclusion, patients with HF and ESRD admitted for NSTEMI experienced lower in-hospital mortality with PCI in comparison with medical therapy only. Invasive percutaneous revascularization may be reasonable for appropriately selected patients with HF and ESRD but randomized controlled trials are needed to determine its safety and efficacy in this high-risk population.

Assessment of the Utilization of Validated Diagnostic Predictive Tools and D-Dimer in the Evaluation of Pulmonary Embolism: A Single-Center Retrospective Cohort Study from a Public Hospital in New York City.

INTRODUCTION: A significant increase in the use of computed tomography with pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism (PE) has been observed in the past twenty years. We aimed to investigate whether the validated diagnostic predictive tools and D-dimers were adequately utilized in a large public hospital in New York City. METHODS: We conducted a retrospective review of patients who underwent CTPA for the specific indication of ruling out PE over a period of one year. Two independent reviewers, blinded to each other and to the CTPA and D-dimer results, estimated the clinical probability (CP) of PE using Well's score, the YEARS algorithm, and the revised Geneva score. Patients were classified based on the presence or absence of PE in the CTPA. RESULTS: A total of 917 patients were included in the analysis (median age: 57 years, female: 59%). The clinical probability of PE was considered low by both independent reviewers in 563 (61.4%), 487 (55%), and 184 (20.1%) patients based on Well's score, the YEARS algorithm, and the revised Geneva score, respectively. D-dimer testing was conducted in less than half of the patients who were deemed to have low CP for PE by both independent reviewers. Using a D-dimer cut-off of <500 ng/mL or the age-adjusted cut-off in patients with a low CP of PE would have missed only a small number of mainly subsegmental PE. All three tools, when combined with D-dimer < 500 ng/mL or 95%. CONCLUSION: All three validated diagnostic predictive tools were found to have significant diagnostic value in ruling out PE when combined with a D-dimer cut-off of <500 ng/mL or the age-adjusted cut-off. Excessive use of CTPA was likely secondary to suboptimal use of diagnostic predictive tools.

Obesity and Peripheral Artery Disease: Current Evidence and Controversies.

PURPOSE OF REVIEW: Obesity is a significant public health problem and a major risk factor for the development and progression of atherosclerosis and its cardiovascular manifestations. Lower extremity peripheral artery disease (PAD) affects 3%-10% of the Western population and, if left untreated, can lead to devastating outcomes with both an increased risk of morbidity and mortality. Interestingly, the association between obesity and PAD remains debatable. Whereas it is well known that PAD and obesity frequently overlap in the same patients, many studies have demonstrated a negative association between obesity and PAD and a protective effect of obesity on disease development and progression, a phenomenon described as the "obesity paradox." Possible mechanisms for this paradox may include genetic background, as assessed by mendelian randomization studies, adipose tissue dysfunction, and body fat distribution rather than adiposity, while other factors, such as sex, ethnicity, sarcopenia in the elderly population, or aggressive treatment of co-existing metabolic conditions in individuals with obesity compared to those with normal weight, could have some impact as well. RECENT RINDINGS: Few reviews and meta-analyses examining systematically the relationship between obesity and PAD exist. The impact of PAD development due to the presence of obesity remains largely controversial. However, the most current evidence, backed by a recent meta-analysis, suggests a potential protective role of a higher body mass index on PAD-related complications and mortality. In this review, we discuss the association between obesity and PAD development, progression, and management, and the potential pathophysiologic mechanisms linking the two diseases.

Ethnic and sex-based differences in outcomes after out-of-hospital cardiac arrest: a glimpse of the largest municipal healthcare system in the United States.

Background: Ethnic and sex-based disparity in outcomes after out-of-hospital cardiac arrest (OHCA) may exist and could be due to social factors and inequality in care. We aimed to study whether ethnic and sex-based differences in out-of-hospital cardiac arrest outcomes occurred in a safety net hospital within the largest municipal healthcare system in the United States. Methods: We conducted a retrospective cohort study of patients successfully resuscitated from an OHCA and brought to New York City Health + Hospitals/Jacobi, from January 2019 to September 2021. Out-of-hospital cardiac arrest characteristics, do not resuscitate and withdrawal of life-sustaining therapy orders, and disposition data were collected and analyzed using regression models. Results: Out of 648 patients screened, 154 were included (48.1% women). On multivariable analysis, sex [odds ratio (OR): 0.84; 95% CI: 0.30-2.4; P=0.74] and ethnic background (OR: 0.80; 95% CI: 0.58-1.12; P=0.196) did not predict discharge survival. No significant sex difference in do not resuscitate (P=0.76) or withdrawal of life-sustaining therapy (P=0.39) orders was found. Younger age (OR: 0.96; P=0.04) and initial shockable rhythm (OR: 7.26; P=0.01) independently predicted survival, both at discharge and at one year. Conclusions: Among patients resuscitated after an out-of-hospital cardiac arrest, neither sex nor ethnic background predicted discharge survival and no sex differences in end-of-life preferences were found. These findings are distinct from those of previously published reports. Given the unique population studied, distinct from those of registry-based studies, socioeconomic factors likely served as bigger drivers of out-of-hospital cardiac arrest outcomes rather than ethnic background or sex.

Plasma extracellular vesicle transcriptome as a dynamic liquid biopsy in acute heart failure.

Background: Acute decompensation is associated with increased mortality in heart failure (HF) patients, though the underlying etiology remains unclear. Extracellular vesicles (EVs) and their cargo may mark specific cardiovascular physiologic states. We hypothesized that EV transcriptomic cargo, including long non-coding RNAs (lncRNAs) and mRNAs, is dynamic from the decompensated to recompensated HF state, reflecting molecular pathways relevant to adverse remodeling. Methods: We examined differential RNA expression from circulating plasma extracellular RNA in acute HF patients at hospital admission and discharge alongside healthy controls. We leveraged different exRNA carrier isolation methods, publicly available tissue banks, and single nuclear deconvolution of human cardiac tissue to identify cell and compartment specificity of the topmost significantly differentially expressed targets. EV-derived transcript fragments were prioritized by fold change (-1.5 to + 1.5) and significance (<5% false discovery rate), and their expression in EVs was subsequently validated in 182 additional patients (24 control; 86 HFpEF; 72 HFrEF) by qRT-PCR. We finally examined the regulation of EV-derived lncRNA transcripts in human cardiac cellular stress models. Results: We identified 138 lncRNAs and 147 mRNAs (present mostly as fragments in EVs) differentially expressed between HF and control. Differentially expressed transcripts between HFrEF vs. control were primarily cardiomyocyte derived, while those between HFpEF vs. control originated from multiple organs and different (non-cardiomyocyte) cell types within the myocardium. We validated 5 lncRNAs and 6 mRNAs to differentiate between HF and control. Of those, 4 lncRNAs (AC092656.1, lnc-CALML5-7, LINC00989, RMRP) were altered by decongestion, with their levels independent of weight changes during hospitalization. Further, these 4 lncRNAs dynamically responded to stress in cardiomyocytes and pericytes in vitro , with a directionality mirroring the acute congested state. Conclusion: Circulating EV transcriptome is significantly altered during acute HF, with distinct cell and organ specificity in HFpEF vs. HFrEF consistent with a multi-organ vs. cardiac origin, respectively. Plasma EV-derived lncRNA fragments were more dynamically regulated with acute HF therapy independent of weight change (relative to mRNAs). This dynamicity was further demonstrated with cellular stress in vitro . Prioritizing transcriptional changes in plasma circulating EVs with HF therapy may be a fruitful approach to HF subtype-specific mechanistic discovery. CLINICAL PERSPECTIVE: What is new?: We performed extracellular transcriptomic analysis on the plasma of patients with acute decompensated heart failure (HFrEF and HFpEF) before and after decongestive efforts.Long non-coding RNAs (lncRNAs) within extracellular vesicles (EVs) changed dynamically upon decongestion in concordance with changes within human iPSC-derived cardiomyocytes under stress.In acute decompensated HFrEF, EV RNAs are mainly derived from cardiomyocytes, whereas in HFpEF, EV RNAs appear to have broader, non-cardiomyocyte origins.What are the clinical implications?: Given their concordance between human expression profiles and dynamic in vitro responses, lncRNAs within EVs during acute HF may provide insight into potential therapeutic targets and mechanistically relevant pathways. These findings provide a "liquid biopsy" support for the burgeoning concept of HFpEF as a systemic disorder extending beyond the heart, as opposed to a more cardiac-focused physiology in HFrEF.

Outcomes of catheter ablation of atrial tachyarrhythmia guided exclusively by activation mapping.

INTRODUCTION: Complex atrial tachyarrhythmias (CATs) are commonly observed in patients with prior catheter ablation or cardiac surgery. These arrhythmias are challenging to map and ablate. Historically, entrainment mapping was utilized to characterize CAT. With the advent of high-definition mapping (HDM), full visualization of the CAT circuit is possible which may obviate the need for entrainment mapping. METHODS: We sought to investigate the outcomes of catheter ablation of CAT guided only by HDM. Consecutive patients who underwent CAT ablation from 2017 to 2021 were included in our study (excluding right atrial tachyarrhythmias). Patients were sorted by the type of mapping performed. Group I consisted of patients where HDM alone was utilized with no attempt of entrainment. Group II consisted of patients where both entrainment and HDM were utilized. RESULTS: A total of 67 patients were included in our study, with 40 patients in HDM group (I) and 27 patients in entrainment group (II). No statistically significant difference regarding 1-year freedom from atrial arrhythmias was found between the two groups (80% vs 77.8%, p = 0.819). Four CATs were terminated by entrainment during procedure versus none in the HDM-only group (p = 0.011). CONCLUSIONS: CAT ablation with HDM alone yielded similar 1-year freedom from atrial arrhythmias compared to ablation with HDM and entrainment. Entrainment combined with HDM was associated with higher undesired CAT interruption rate. Further validation is needed with randomized control trials.

Expanding the horizon of EV-RNAs: LncRNAs in EVs as biomarkers for disease pathways.

Extracellular vesicles (EVs) are membrane-bound nanoparticles with different types of cargo released by cells and postulated to mediate functions such as intercellular communications. Recent studies have shown that long non-coding RNAs (lncRNAs) or their fragments are present as cargo within EVs. LncRNAs are a heterogeneous group of RNA species with a length exceeding 200 nucleotides with diverse functions in cells based on their localization. While lncRNAs are known for their important functions in cellular regulation, their presence and role in EVs have only recently been explored. While certain studies have observed EV-lncRNAs to be tissue-and disease-specific, it remains to be determined whether or not this is a global observation. Nonetheless, these molecules have demonstrated promising potential to serve as new diagnostic and prognostic biomarkers. In this review, we critically evaluate the role of EV-derived lncRNAs in several prevalent diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases, with a specific focus on their role as biomarkers.